Kidneys are one of the targets for SARS-CoV-2, it is reported that up to 36% of patients with SARS-CoV-2 infection would develop into acute kidney injury (AKI). AKI is associated with high mortality in the clinical setting and contributes to the transition of AKI to chronic kidney disease (CKD). Up to date, the underlying mechanisms are obscure and there is no effective and specific treatment for COVID-19-induced AKI. In the present study, we investigated the mechanisms and interactions between Quercetin and SARS-CoV-2 targets proteins by using network pharmacology and molecular docking. The renal protective effects of Quercetin on COVID-19-induced AKI may be associated with the blockade of the activation of inflammatory, cell apoptosis-related signaling pathways. Quercetin may also serve as SARS-CoV-2 inhibitor by binding with the active sites of SARS-CoV-2 main protease 3CL and ACE2, therefore suppressing the functions of the proteins to cut the viral life cycle. In conclusion, Quercetin may be a novel therapeutic agent for COVID-19-induced AKI. Inhibition of inflammatory, cell apoptosis-related signaling pathways may be the critical mechanisms by which Quercetin protects kidney from SARS-CoV-2 injury.

Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a secretory serine protease synthesized primarily by the liver. It mainly promotes the degradation of low-density lipoprotein receptor (LDL-R) by binding LDL-R, reducing low-density lipoprotein cholesterol (LDL-C) clearance. In addition to regulating LDL-R, PCSK9 inhibitors can also bind Toll-like receptors (TLRs), scavenger receptor B (SR-B/CD36), low-density lipoprotein receptor-related protein 1 (LRP1), apolipoprotein E receptor-2 (ApoER2) and very-low-density lipoprotein receptor (VLDL-R) reducing the lipoprotein concentration and slowing thrombosis. In addition to cardiovascular diseases, PCSK9 is also used in pancreatic cancer, sepsis, and Parkinson’s disease. Currently marketed PCSK9 inhibitors include alirocumab, evolocumab, and inclisiran, as well as small molecules, nucleic acid drugs, and vaccines under development. This review systematically summarized the application, preclinical studies, safety, mechanism of action, and latest research progress of PCSK9 inhibitors, aiming to provide ideas for the drug research and development and the clinical application of PCSK9 in cardiovascular diseases and expand its application in other diseases.

Extracellular vesicles (EVs), as natural carriers, are regarded as a new star in nanomedicine due to their excellent biocompatibility, fascinating physicochemical properties, and unique biological regulatory functions. However, there are still some challenges to using natural EVs, including poor targeting ability and the clearance from circulation, which may limit their further development and clinical use. Nucleic acid has the functions of programmability, targeting, gene therapy, and immune regulation. Owing to the engineering design and modification by integrating functional nucleic acid, EVs offer excellent performances as a therapeutic system in vivo. This review briefly introduces the function and mechanism of nucleic acid in the diagnosis and treatment of diseases. Then, the strategies of nucleic acid-functionalized EVs are summarized and the latest progress of nucleic acid-functionalized EVs in nanomedicine is highlighted. Finally, the challenges and prospects of nucleic acid-functionalized EVs as a promising diagnostic system are proposed.

Acute myocardial infarction is a major global health problem, and the repair of damaged myocardium is still a major challenge. Myocardial injury triggers an inflammatory response: immune cells infiltrate into the myocardium while activating myofibroblasts and vascular endothelial cells, promoting tissue repair and scar formation. Fragments released by cardiomyocytes become endogenous “danger signals”, which are recognized by cardiac pattern recognition receptors, activate resident cardiac immune cells, release thrombin factors and inflammatory mediators, and trigger severe inflammatory responses. Inflammatory signaling plays an important role in the dilation and fibrosis remodeling of the infarcted heart, and is a key event driving the pathogenesis of post-infarct heart failure. At present, there is no effective way to reverse the inflammatory microenvironment in injured myocardium, so it is urgent to find new therapeutic and diagnostic strategies. Nanomedicine, the application of nanoparticles for the prevention, treatment, and imaging of disease, has produced a number of promising applications. This review discusses the treatment and challenges of myocardial injury and describes the advantages of functional nanoparticles in regulating the myocardial inflammatory microenvironment and overcoming side effects. In addition, the role of inflammatory signals in regulating the repair and remodeling of infarcted hearts is discussed, and specific therapeutic targets are identified to provide new therapeutic ideas for the treatment of myocardial injury.

Objective: The present study aims to provide evidence on the potential protective role of Salvia miltiorrhiza Bunge (Danshen) and its bioactive compound Tanshinone IIA (TanIIA) in AKI and to reveal the specific regulatory function of PXR/NF-κB signaling in AKI-induced renal inflammation.Methods: A network pharmacological analysis was used to study target genes and regulatory networks in the treatment of Salvia miltiorrhiza on AKI. Further experiments with in vivo AKI mouse model and in vitro studies were applied to investigate the renal protective effect of TanIIA in AKI. The mechanisms of TanIIA regulating PXR/NF-κB signaling in renal inflammation were also studied.Results: Network pharmacology had suggested the nuclear receptor family as new therapeutic targets of Salvia miltiorrhiza in AKI treatment. The in vivo studies had demonstrated that TanIIA improved renal function and inflammation by reducing necrosis and promoting the proliferation of tubular epithelial cells. Improved renal arterial perfusion in AKI mice with TanIIA treatment was also recorded by ultrasonography. In vitro studies had shown that TanIIA ameliorated renal inflammation by activating the PXR while inhibiting PXR-mediated NF-κB signaling. The results had suggested a role of PXR activation against AKI-induced renal inflammation.Conclusion:Salvia miltiorrhiza Bunge (Danshen) may protect the kidneys against AKI by regulating nuclear receptors. TanIIA improved cell necrosis proliferation and reduced renal inflammation by upregulating the expression of the PXR and inhibiting NF-κB signaling in a PXR-dependent manner. The PXR may be a potential therapeutic target for AKI treatment.